SI9520153B - Human DNase I variants - Google Patents

Human DNase I variants Download PDF

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Publication number
SI9520153B
SI9520153B SI9520153A SI9520153A SI9520153B SI 9520153 B SI9520153 B SI 9520153B SI 9520153 A SI9520153 A SI 9520153A SI 9520153 A SI9520153 A SI 9520153A SI 9520153 B SI9520153 B SI 9520153B
Authority
SI
Slovenia
Prior art keywords
human dnase
amino acid
actin
variant
acid sequence
Prior art date
Application number
SI9520153A
Other languages
Slovenian (sl)
Other versions
SI9520153A (en
Inventor
Robert A. Lazarus
Steven Shak
Jana S. Ulmer
Original Assignee
Genentech, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Application filed by Genentech, Inc. filed Critical Genentech, Inc.
Publication of SI9520153A publication Critical patent/SI9520153A/en
Publication of SI9520153B publication Critical patent/SI9520153B/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases RNAses, DNAses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/12—Mucolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to amino acid sequence variants of human DNase I that have reduced binding affinity for actin. The invention provides nucleic acid sequences encoding such actin-resistant variants, thereby enabling the production of these variants in quantities sufficient for clinical use. The invention also relates to pharmaceutical compositions and therapeutic uses of actin-resistant variants of human DNase I.

Claims (12)

1 Patentni zahtevki 1. Proti aktinu odporna varianta humane DNaze I, ki ima DNA hidrolitično aktivnost, vezavno afiniteto za aktin, kije manjša od vezavne afinitete za aktin nativne humane DNaze I, in aminokislinsko sekvenco, ki ima vsaj 90 % identičnost z aminokislinsko sekvenco nativne humane DNaze I, prikazane na sl. 1.A patentable claim 1 against an actin-resistant human DNase I human having a DNA hydrolytic activity, a binding affinity for actin less than the binding affinity for actinin native human DNase I, and an amino acid sequence having at least 90% identity with the amino acid sequence of native human DNase I, shown in FIG. 1. 2. Proti aktinu odporna varianta humane DNaze I po zahtevku 1, ki obsega aminokislinsko sekvenco, ki ima vsaj 95 % identičnost z aminokislinsko sekvenco nativne humane DNaze I, prikazane na sl. 1.An anti-actin-resistant human DNase I version according to claim 1 comprising an amino acid sequence having at least 95% identity with the amino acid sequence of the native human DNase I shown in FIG. 1. 3. Proti aktinu odporna varianta humane DNaze I po zahtevku 1 ali 2, ki ima vsaj eno aminokislinsko substitucijo za drugo pri enem ali večih naslednjih položajih: His44, Leu45, Val48, Gly49, Leu52, Asp53, Asn56, His64, Tyr65, Val66, Val67, Glu69 ali Alal 14.3. An actin-resistant human DNase I variant of claim 1 or claim 2 having at least one amino acid substitution for the other at one or more of the following positions: His44, Leu45, Val48, Gly49, Leu52, Asp53, Asn56, His64, Tyr65, Val66, Val67, Glu69 or Alal 14. 4. Proti aktinu odporna varianta humane DNaze I po zahtevku 3, ki ima aminokislinsko substitucijo za drugo pri enem od navedenih položajev.An anti-actin-resistant human DNase I variant of claim 3 having an amino acid substitution for the other at one of said positions. 5. Proti aktinu odporna varianta humane DNaze I po zahtevku 1, ki ima aminokislinsko sekvenco, ki se razlikuje od aminokislinske sekvence, prikazane na sl. 1, z le eno aminokislinsko substitucijo pri enem ali večih izmed naslednjih položajev: His44, Leu45, Val48, Gly49, Leu52, Asp53, Asn56, His64, Tyr65, Val66, Val67, Glu69 ali Alal14. 2An anti-actin-resistant human DNase I variant of claim 1 having an amino acid sequence different from the amino acid sequence shown in FIG. 1, with only one amino acid substitution at one or more of the following positions: His44, Leu45, Val48, Gly49, Leu52, Asp53, Asn56, His64, Tyr65, Val66, Val67, Glu69 or Alal14. 2 6. Proti aktinu odporna varianta humane DNaze I po kateremkoli od zahtevkov 3-5, kjer aminokislinska substitucija ustvari glikozilacijsko mesto znotraj navedene variante, ki ni prisotno v nativni humani DNazi I.An anti-actin-resistant human DNase I version according to any one of claims 3-5, wherein the amino acid substitution generates a glycosylation site within said variant not present in native human DNase I. 7. Izolirana nukleinska kislina, ki kodira proti aktinu odporno varianto humane DNaze I po kateremkoli od zahtevkov 1 do 6.An isolated nucleic acid encoding an actin-resistant human DNase I variant according to any one of claims 1 to 6. 8. Uporaba variante humane DNaze I po kateremkoli od zahtevkov 1 do 6 v izdelavi zdravila za zdravljenje cistične fibroze.Use of a human DNase I variant according to any one of claims 1 to 6 in the manufacture of a medicament for the treatment of cystic fibrosis. 9. Uporaba variante humane DNaze I po kateremkoli od zahtevkov 1 do 6 v izdelavi zdravila za zdravljenje kroničnega bronhitisa.Use of a human DNase I variant according to any one of claims 1 to 6 in the manufacture of a medicament for the treatment of chronic bronchitis. 10. Farmacevtski sestavek, ki obsega varianto humane DNaze I po kateremkoli od zahtevkov 1 - 6 in, po izbiri, farmacevtsko sprejemljiv ekscipient.A pharmaceutical composition comprising a variant of human DNase I according to any one of claims 1-6 and, optionally, a pharmaceutically acceptable excipient. 11. Sestavek po zahtevku 10, kjer je sestavek v tekoči obliki.The composition of claim 10, wherein the composition is in liquid form. 12. Sestavek po zahtevku 10, kjer je sestavek v obliki prahu.The composition of claim 10, wherein the composition is in the form of a powder.
SI9520153A 1995-02-24 1995-02-24 Human DNase I variants SI9520153B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1995/002366 WO1996026278A1 (en) 1995-02-24 1995-02-24 HUMAN DNase I VARIANTS

Publications (2)

Publication Number Publication Date
SI9520153A SI9520153A (en) 1998-06-30
SI9520153B true SI9520153B (en) 2004-10-31

Family

ID=22248728

Family Applications (1)

Application Number Title Priority Date Filing Date
SI9520153A SI9520153B (en) 1995-02-24 1995-02-24 Human DNase I variants

Country Status (22)

Country Link
EP (1) EP0811068B1 (en)
JP (1) JPH11505408A (en)
AT (1) ATE230027T1 (en)
AU (1) AU720635B2 (en)
BG (1) BG64061B1 (en)
BR (1) BR9510323A (en)
CA (1) CA2210871C (en)
CZ (1) CZ288633B6 (en)
DE (1) DE69529235T2 (en)
DK (1) DK0811068T3 (en)
ES (1) ES2188653T3 (en)
HU (1) HU223272B1 (en)
MX (1) MX9706428A (en)
NO (1) NO326612B1 (en)
PL (1) PL180773B1 (en)
PT (1) PT811068E (en)
RU (1) RU2215787C2 (en)
SI (1) SI9520153B (en)
SK (1) SK283850B6 (en)
UA (2) UA66749C2 (en)
WO (1) WO1996026278A1 (en)
ZA (1) ZA961419B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SK284191B6 (en) * 1995-02-24 2004-10-05 Genentech, Inc. Human DNASE I variants
US6391607B1 (en) * 1996-06-14 2002-05-21 Genentech, Inc. Human DNase I hyperactive variants
EP1433842B1 (en) 2002-12-18 2011-01-05 Roche Diagnostics GmbH Recombinant bovine pancreatic desoxyribonuclease I with high specific activity
US7118901B2 (en) 2002-12-18 2006-10-10 Roche Diagnostics Operations, Inc. Recombinant bovine pancreatic desoxyribonuclease I with high specific activity
US20150010527A1 (en) 2012-02-01 2015-01-08 Protalix Ltd. Dnase i polypeptides, polynucleotides encoding same, methods of producing dnase i and uses thereof in therapy

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE68929551T2 (en) * 1988-12-23 2008-03-06 Genentech, Inc., South San Francisco Human DNase
US5464817A (en) * 1990-04-11 1995-11-07 Brigham And Women's Hospital Method for reducing the viscosity of pathological mucoid airway contents in the respiratory tract comprising administering actin-binding compounds with or without DNASE I

Also Published As

Publication number Publication date
CA2210871C (en) 2009-04-07
ES2188653T3 (en) 2003-07-01
SI9520153A (en) 1998-06-30
ZA961419B (en) 1997-08-22
DK0811068T3 (en) 2003-03-10
UA65523C2 (en) 2004-04-15
SK114797A3 (en) 1998-02-04
CA2210871A1 (en) 1996-08-29
AU720635B2 (en) 2000-06-08
AU1970395A (en) 1996-09-11
SK283850B6 (en) 2004-03-02
NO326612B1 (en) 2009-01-19
PL180773B1 (en) 2001-04-30
WO1996026278A1 (en) 1996-08-29
NO973876L (en) 1997-10-24
BG101846A (en) 1998-07-31
MX9706428A (en) 1997-11-29
NO973876D0 (en) 1997-08-22
HU223272B1 (en) 2004-04-28
EP0811068A1 (en) 1997-12-10
HUT77422A (en) 1998-04-28
RU2215787C2 (en) 2003-11-10
CZ267797A3 (en) 1998-01-14
BG64061B1 (en) 2003-11-28
ATE230027T1 (en) 2003-01-15
DE69529235D1 (en) 2003-01-30
PL321890A1 (en) 1997-12-22
PT811068E (en) 2003-04-30
UA66749C2 (en) 2004-06-15
CZ288633B6 (en) 2001-08-15
EP0811068B1 (en) 2002-12-18
DE69529235T2 (en) 2003-09-04
JPH11505408A (en) 1999-05-21
BR9510323A (en) 1997-11-11

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